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Updated: May 10, 2026
Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Gene delivery with active targeting to ovarian cancer cells mediated by folate receptor alpha
Zhiyao He1, Yiyi Yu, Ying Zhang
1State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Abstract:
Folate receptor alpha (FRalpha) is overexpressed on ovarian cancer cells and is a promising molecular target for ovarian cancer gene therapy, but there was still no related report. In this study, folate modified cationic liposomes (F-PEG-CLPs) for ovarian cancer gene delivery were developed for the first time. Folate-poly(ethylene glycol)-succinate-cholesterol (F-PEG-suc-Chol) was firstly synthesized and then used to prepare folate-targeted cationic liposomes/plasmid DNA complexes (F-targeted lipoplexes). F-targeted lipoplexes were prepared by post-insertion method, and displayed membrane structure by transmission electron microscopy observation with the diameter of 193 nm-200 nm and the zeta potential of 35 mV-38 mV. DNase degradation experiments showed that plasmid DNA could be effectively shielded by F-targeted lipoplexes in vitro. F-targeted lipoplexes could transfer gene into human ovarian carcinoma cell line SKOV-3, and 0.1% F-PEG-CLPs composed by DOTAP/Chol/mPEG-Chol/F-PEG-suc-Chol (50:45:5:0.1, molar ratio) had the highest transfection efficiency. The transfection activity of F-targeted lipoplexes could be competitively inhibited by free folic acid, demonstrating that folate-FRalpha interaction caused high transfection efficiency of F-targeted lipoplexes. The uptake mechanism of F-targeted lipoplexes was further validated on human oral carcinoma cell line KB and human liver carcinoma cell line HepG2. The concentration-dependent and time-dependent cytotoxicity of targeted material F-PEG-suc-Chol was observed by MTT assay on SKOV-3 cell and its application would not increase the cytotoxicity of F-targeted lipoplexes in SKOV-3 cells. All the data indicated that F-PEG-CLPs would be a promising gene vector targeting for ovarian cancer therapy.
Insights
Researchers developed novel folate-targeted cationic liposomes for ovarian cancer gene therapy. These F-PEG-CLPs effectively deliver genes to cancer cells via folate receptor alpha, showing promise for targeted ovarian cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Folate receptor alpha (FRalpha) is overexpressed on ovarian cancer cells, presenting a potential target for gene therapy.
- Previous research lacked reports on targeted gene delivery systems for ovarian cancer using FRalpha.
Purpose of the Study:
- To develop and characterize novel folate-modified cationic liposomes (F-PEG-CLPs) for targeted ovarian cancer gene delivery.
- To evaluate the efficacy and safety of F-PEG-CLPs in delivering genes to ovarian cancer cells.
Main Methods:
- Synthesis of folate-poly(ethylene glycol)-succinate-cholesterol (F-PEG-suc-Chol) and preparation of folate-targeted cationic liposomes/plasmid DNA complexes (F-targeted lipoplexes) via post-insertion.
- Characterization of F-targeted lipoplexes using transmission electron microscopy and zeta potential measurements.
- In vitro assessment of plasmid DNA shielding, gene transfection efficiency in SKOV-3 cells, competitive inhibition studies with free folic acid, and cytotoxicity assays (MTT).
Main Results:
- F-targeted lipoplexes exhibited a suitable size (193-200 nm) and zeta potential (35-38 mV), effectively shielding plasmid DNA.
- Optimal transfection efficiency was achieved with 0.1% F-PEG-CLPs (DOTAP/Chol/mPEG-Chol/F-PEG-suc-Chol, 50:45:5:0.1 molar ratio) in SKOV-3 cells.
- Folate receptor-mediated uptake was confirmed by competitive inhibition with folic acid and validated in KB and HepG2 cell lines.
- The targeted material F-PEG-suc-Chol did not increase the cytotoxicity of F-targeted lipoplexes in SKOV-3 cells.
Conclusions:
- Folate-modified cationic liposomes (F-PEG-CLPs) represent a novel and effective gene delivery vector for ovarian cancer.
- The targeted delivery mechanism relies on the interaction between folate and folate receptor alpha, enhancing transfection efficiency.
- F-PEG-CLPs demonstrate potential as a safe and promising therapeutic strategy for ovarian cancer gene therapy.
